Biomarkers.

Background: The measurement of serum and cerebrospinal fluid (CSF) neurofilaments light chain (NfLs) has been proven promising in differentiating the behavioral variant frontotemporal dementia (bvFTD) from non-neurodegenerative mimics, including primary psychiatric disorders and non-progressive cognitive/behavioral changes. However, studies on this topic are based on clinical diagnosis, which remains challenging and potentially confounded by the overlapping clinical phenotypes. We investigated the role of NfLs in this field by classifying patients based on the presence/absence of pathological longitudinal brain volume changes.

Utility of icobrain for brain volumetry in multiple sclerosis clinical practice.

Background: Few studies on multiple sclerosis (MS) have explored the variability of percentage brain volume change (PBVC) measurements obtained from different clinical MRIs. In a retrospective multicentre cohort study, we quantified the variability of annualised PBVC in clinical MRIs.

Methods: Clinical MRIs of relapse-onset MS patients were assessed by icobrain.

Hippocampal atrophy and white matter lesions characteristics can predict evolution to dementia in patients with vascular mild cognitive impairment.

Background: Vascular mild cognitive impairment (VMCI) is a transitional condition that may evolve into Vascular Dementia(VaD). Hippocampal volume (HV) is suggested as an early marker for VaD, the role of white matter lesions (WMLs) in neurodegeneration remains debated.

Objectives: Evaluate HV and WMLs as predictive markers of VaD in VMCI patients by assessing: (i)baseline differences in HV and WMLs between converters to VaD and non-converters, (ii) predictive power of HV and WMLs for VaD, (iii) associations between HV, WMLs, and cognitive decline, (iv)the role of WMLs on HV.

Grey Matter Atrophy and its Relationship with White Matter Lesions in Patients with Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease, Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder, and Multiple Sclerosis.

Objective: To evaluate: (1) the distribution of gray matter (GM) atrophy in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD), and relapsing-remitting multiple sclerosis (RRMS); and (2) the relationship between GM volumes and white matter lesions in various brain regions within each disease.

Methods: A retrospective, multicenter analysis of magnetic resonance imaging data included patients with MOGAD/AQP4+NMOSD/RRMS in non-acute disease stage. Voxel-wise analyses and general linear models were used to evaluate the relevance of regional GM atrophy.

Regional hippocampal atrophy reflects memory impairment in patients with early relapsing remitting multiple sclerosis.

Background: Research work has shown that hippocampal subfields are atrophic to varying extents in multiple sclerosis (MS) patients. However, studies examining the functional implications of subfield-specific hippocampal damage in early MS are limited. We aim to gain insights into the relationship between hippocampal atrophy and memory function by investigating the correlation between global and regional hippocampal atrophy and memory performance in early MS patients.

Determinants and Biomarkers of Progression Independent of Relapses in Multiple Sclerosis.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) suggests that a smoldering inflammatory activity is present from the earliest stages of the disease and underlies the progression of disability, which proceeds relentlessly and independently of clinical and radiological relapses (PIRA). The complex system of pathological events driving "chronic" worsening is likely linked with the early accumulation of compartmentalized inflammation within the central nervous system as well as insufficient repair phenomena and mitochondrial failure. These mechanisms are partially lesion-independent and differ from those causing clinical relapses and the formation of new focal demyelinating lesions; they lead to neuroaxonal dysfunction and death, myelin loss, glia alterations, and finally, a neuronal network dysfunction outweighing central nervous system (CNS) compensatory mechanisms.

Disease progression in the first 5 years of treatment in multiple sclerosis: Predictive value of early brain and lesion volume changes.

Background: Whether the degree of inflammation (and its resolution) and neurodegeneration after treatment initiation predicts disease progression in multiple sclerosis (MS) remains unclear.

Objectives: To assess the predictive value of magnetic resonance imaging (MRI)-derived brain and lesion volume (LV) changes in years 1 and 2 of treatment for disease progression.

Methods: Patients receiving early interferon beta-1a treatment in REFLEX/REFLEXION ( = 262) were included.

BIANCA-MS: An optimized tool for automated multiple sclerosis lesion segmentation.

In this work we present BIANCA-MS, a novel tool for brain white matter lesion segmentation in multiple sclerosis (MS), able to generalize across both the wide spectrum of MRI acquisition protocols and the heterogeneity of manually labeled data. BIANCA-MS is based on the original version of BIANCA and implements two innovative elements: a harmonized setting, tested under different MRI protocols, which avoids the need to further tune algorithm parameters to each dataset; and a cleaning step developed to improve consistency in automated and manual segmentations, thus reducing unwanted variability in output segmentations and validation data. BIANCA-MS was tested on three datasets, acquired with different MRI protocols.

The spatio-temporal relationship between concurrent lesion and brain atrophy changes in early multiple sclerosis: A post-hoc analysis of the REFLEXION study.

Background: White matter (WM) lesions and brain atrophy are present early in multiple sclerosis (MS). However, their spatio-temporal relationship remains unclear.

Methods: Yearly magnetic resonance images were analysed in 387 patients with a first clinical demyelinating event (FCDE) from the 5-year REFLEXION study.

Serum Glial Fibrillary Acidic Protein Compared With Neurofilament Light Chain as a Biomarker for Disease Progression in Multiple Sclerosis.

Importance: There is a lack of validated biomarkers for disability progression independent of relapse activity (PIRA) in multiple sclerosis (MS).

Objective: To determine how serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) correlate with features of disease progression vs acute focal inflammation in MS and how they can prognosticate disease progression.

Design, Setting, And Participants: Data were acquired in the longitudinal Swiss MS cohort (SMSC; a consortium of tertiary referral hospitals) from January 1, 2012, to October 20, 2022.

Methods for Brain Atrophy MR Quantification in Multiple Sclerosis: Application to the Multicenter INNI Dataset.

Background: Current therapeutic strategies in multiple sclerosis (MS) target neurodegeneration. However, the integration of atrophy measures into the clinical scenario is still an unmet need.

Purpose: To compare methods for whole-brain and gray matter (GM) atrophy measurements using the Italian Neuroimaging Network Initiative (INNI) dataset.

Assessing COVID-19-Related Excess Mortality Using Multiple Approaches-Italy, 2020-2021.

Introduction: Excess mortality (EM) is a valid indicator of COVID-19's impact on public health. Several studies regarding the estimation of EM have been conducted in Italy, and some of them have shown conflicting values. We focused on three estimation models and compared their results with respect to the same target population, which allowed us to highlight their strengths and limitations.

Clinical and MRI measures to identify non-acute MOG-antibody disease in adults.

MRI and clinical features of myelin oligodendrocyte glycoprotein (MOG)-antibody disease may overlap with those of other inflammatory demyelinating conditions posing diagnostic challenges, especially in non-acute phases and when serologic testing for MOG antibodies is unavailable or shows uncertain results. We aimed to identify MRI and clinical markers that differentiate non-acute MOG-antibody disease from aquaporin 4 (AQP4)-antibody neuromyelitis optica spectrum disorder and relapsing remitting multiple sclerosis, guiding in the identification of patients with MOG-antibody disease in clinical practice. In this cross-sectional retrospective study, data from 16 MAGNIMS centres were included.

Resting-state functional MRI in multicenter studies on multiple sclerosis: a report on raw data quality and functional connectivity features from the Italian Neuroimaging Network Initiative.

The Italian Neuroimaging Network Initiative (INNI) is an expanding repository of brain MRI data from multiple sclerosis (MS) patients recruited at four Italian MRI research sites. We describe the raw data quality of resting-state functional MRI (RS-fMRI) time-series in INNI and the inter-site variability in functional connectivity (FC) features after unified automated data preprocessing. MRI datasets from 489 MS patients and 246 healthy control (HC) subjects were retrieved from the INNI database.

The spatio-temporal relationship between white matter lesion volume changes and brain atrophy in clinically isolated syndrome and early multiple sclerosis.

Background: White matter lesions and brain atrophy are both present early in multiple sclerosis. However, the spatio-temporal relationship between atrophy and lesion processes remains unclear.

Methods: Yearly magnetic resonance images were analyzed in 392 patients with clinically isolated syndrome from the 5-year REFLEX/REFLEXION studies.

Reduction in grey matter atrophy in patients with relapsing multiple sclerosis following treatment with cladribine tablets.

Background And Purpose: Measures of atrophy in the whole brain can be used to reliably assess treatment effect in clinical trials of patients with multiple sclerosis (MS). Trials assessing the effect of treatment on grey matter (GM) and white matter (WM) atrophy are very informative, but hindered by technical limitations. This study aimed to measure GM and WM volume changes, using a robust longitudinal method, in patients with relapsing MS randomized to cladribine tablets 3.

Multicenter data harmonization for regional brain atrophy and application in multiple sclerosis.

Background: In multiple sclerosis (MS), determination of regional brain atrophy is clinically relevant. However, analysis of large datasets is rare because of the increased variability in multicenter data.

Purpose: To compare different methods to correct for center effects.

[Effects of the COVID-19 pandemic on the inequalities in total mortality by country of birth].

Objectives: to evaluate the impact on total mortality of the COVID-19 pandemic in Italy, by country of birth.

Design: historic cohort study based on administrative databases.

Setting And Participants: the study is based on subjects included in the Base Register of Individuals of the Italian National Institute of Statistics on 01.

Slowly expanding lesions relate to persisting black-holes and clinical outcomes in relapse-onset multiple sclerosis.

Background: Slowly expanding lesions (SELs) are MRI markers of chronic active lesions in multiple sclerosis (MS). T1-hypointense black holes, and reductions in magnetization transfer ratio (MTR) are pathologically correlated with myelin and axonal loss. While all associated with progressive MS, the relationship between these lesion's metrics and clinical outcomes in relapse-onset MS has not been widely investigated.

Association of Brain Atrophy With Disease Progression Independent of Relapse Activity in Patients With Relapsing Multiple Sclerosis.

Importance: The mechanisms driving neurodegeneration and brain atrophy in relapsing multiple sclerosis (RMS) are not completely understood.

Objective: To determine whether disability progression independent of relapse activity (PIRA) in patients with RMS is associated with accelerated brain tissue loss.

Design, Setting, And Participants: In this observational, longitudinal cohort study with median (IQR) follow-up of 3.